HAIFA, Israel—Pluristem Therapeutics Inc. recently presented positive results from a series of studies of its PLX-R18 cell therapy product conducted by the U.S. Department of Defense’s (DoD) Armed Forces Radiobiology Research Institute at the Uniformed Services University of the Health Sciences. The studies were designed to evaluate PLX-R18 as a potential prophylactic countermeasure against acute radiation syndrome (ARS), when administered prior to radiation exposure.
According to Yaky Yanay, Pluristem's president and CEO, “PLX-R18 cell therapy candidate is a product derived from the human placenta ... and is an off-the-shelf product which requires no genetic or tissue matching. PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system; this system creates the blood cells that protect us from infection, uncontrolled bleeding and anemia. As a result, the distinct proteins released stimulate the regeneration of damaged bone marrow to produce blood cells (white, red and platelets).”
“PLX-R18’s unique profile of secreted cytokines affects the maintenance of the hematopoietic niche, the renewal and differentiation of hematopoietic cells, and the mobilization of differentiated blood cells into peripheral blood,” Yanay continues. “Therapeutic proteins secreted by the cells include GCSF, MCP-1, IL-6 and IL-8. Animal studies have shown that PLX-R18 secretes proteins that stimulate damaged bone marrow to secrete endogenous regenerative proteins and recover the ability to produce blood cells.”
Animal studies demonstrate that PLX-R18, administered 24 hours before radiation exposure and again 72 hours after exposure, resulted in a significant increase in survival rates — from 4 percent survival rate in the placebo group to 74 percent in the treated group. The data also show an increase in recovery of blood lineages (platelets, neutrophils, white blood cells and lymphocytes) and a favorable safety profile. Histopathological analysis and hematopoietic progenitor clonogenic assay of collected tissues shows a significant increase in bone marrow cell numbers and improved regenerative capability into all blood lineages.
“We are very pleased with the positive results from the studies showing that PLX-R18 can potentially be used prophylactically, before exposure to radiation. We believe that this outcome is an important contribution to protect the armed and medical forces which may need to enter contaminated areas,” says Yanay. “It is Pluristem’s goal to provide the different federal agencies access to PLX-R18 that it may be used as a countermeasure both before and after radiation exposure in order to minimize hematological and other organ damage.”
In addition to the DoD study, PLX-R18 is also being evaluated by the National Institute of Allergy and Infectious Diseases (NIAID) as a treatment following ARS. Data from these studies demonstrated a significant increase in survival rates and enhanced neutrophil and lymphocyte recovery in radiation subjects.
“The NIAID studies showed that PLX-R18 administration resulted in a statistically significant improvement in the survival rate and recovery of blood cell production in animals exposed to high levels of radiation, and demonstrated the treatment’s mechanism of action. Efficacy measures included survival as well as level of bone marrow function, which is affected by exposure to high levels of radiation as may occur in a nuclear accident or attack,” Yanay adds. “Safety data showed that PLX-R18 cells did not affect non-irradiated animals, suggesting that in scenarios requiring the rapid treatment of large populations, such as in the case of a nuclear emergency, no determination of an individual’s level of exposure would be required prior to treatment.”
He notes, “After reaching an understanding with the FDA on the regulatory pathway needed and conducting additional mechanism studies with the support of the NIH, we have progressed our discussions with the Biomedical Advanced Research and Development Authority to submit a proposal by the end of September, aiming for a study strategically designed to demonstrate the superiority of PLX-R18 versus current standards of care, with the goal of executing a full contract once the study is completed. Another collaboration agreement with the DOD is to study PLX-R18 cell therapy product in the treatment of long-term lung injuries following exposure to mustard gas.”
PLX-R18 has been granted an FDA Orphan Drug Designation and an IND for the treatment of ARS. Yanay also points out that PLX cell therapy has been granted Orphan Drug Designation for the treatment of graft failure and incomplete hematopoietic recovery following HCT.
According to Yanay, “Another medical indication is insufficient recovery after hematopoietic cell transplantation (HCT), which is a standard treatment in various malignant and non-malignant conditions. A significant number of patients do not respond well to the transplantation and may require frequent transfusions, which expose them to transfusion-related risks such as allo-sensitization and infections.”
Regarding a Phase 1 study of PLX-R18 to treat incomplete hematopoietic recovery following HCT, he explains, “The study’s primary endpoint was safety, to address the safety requirement of the animal rule pathway regarding the ARS studies. These partial results demonstrate that PLX-R18 is safe and well tolerated, with no unexpected toxicities. Furthermore, even in the lower doses, the cells appear to regenerate damaged bone marrow, leading to increased production of platelets and red blood cells, ultimately reducing the number of required transfusions—although caution is appropriate in discussing early data with a small number of patients.”
“Pluristem’s PLX-R18 cells are [also] being examined in Fukushima Medical University in Japan for the treatment of hematological ARS and gastrointestinal (GI),” Yanay tells DDNews. “All of these important studies and data so far make us strongly believe that the product has the potential to stimulate the regeneration of damaged bone marrow to produce blood cells while also increasing survival and benefiting additional body systems, suggesting that PLX-R18 has the ability to treat ARS as a multi-organ therapy.”
“We at Pluristem look forward to advancing our ARS program ... We remain committed to completing our ongoing Phase 1 study of PLX-R18 in incomplete hematopoietic recovery following HCT as quickly as possible and will seek to expand PLX-R18 for use with respect to additional medical conditions, with the goal of bringing innovative, safe and effective treatments for patients with a variety of bone marrow deficiency indications,” he concludes.